CASP1 as a potential target of Dendrobium in Sjögren's syndrome: Multi-omics analysis and preliminary experimental evidence.

Sjögren's syndrome is an autoimmune disease that causes dry mouth and dry eyes by attacking the body's moisture-producing glands. Currently, there are limited effective treatments available. Researchers investigated whether Dendrobium, a traditional Chinese herb commonly used in acupuncture and herbal medicine practices, might offer therapeutic benefits for this condition. The study used advanced computer analysis to examine genes and proteins involved in Sjögren's syndrome across multiple datasets from patient tissue samples. They identified a protein called CASP1 that appears significantly elevated in patients with Sjögren's syndrome, particularly in immune cells like monocytes and dendritic cells. CASP1 seems to play a role in creating inflammation in the body. The researchers found that CASP1 levels correlated with certain antibody levels (IgA and IgM) and could potentially serve as a diagnostic marker with 92% accuracy. Computer modeling showed that 6-hydroxy-dendrobine, an active compound in Dendrobium, binds well to the CASP1 protein, suggesting it might help reduce inflammation. Laboratory testing on blood samples from 65 Sjögren's patients confirmed higher CASP1 levels compared to healthy individuals. While these findings are promising and suggest Dendrobium might work through reducing CASP1-related inflammation, the researchers emphasize that this is preliminary computational and observational research. Actual therapeutic effects need to be confirmed through clinical trials before Dendrobium can be recommended as a treatment. If you're considering Chinese herbal medicine or acupuncture for Sjögren's syndrome, consult with a qualified, licensed acupuncturist or Traditional Chinese Medicine practitioner who can assess your individual condition.

This multi-omics study investigated CASP1 as a therapeutic target for Dendrobium in primary Sjögren's syndrome (pSS). Researchers performed meta-analysis on three transcriptomic datasets (GSE40611, GSE143153, GSE66795) identifying 293 differentially expressed genes. Network pharmacology analysis using HERB 2.0 database identified three core candidate genes: CASP1, HSP90AA1, and RPS6KA1. CASP1 demonstrated superior clinical potential with significant upregulation in independent validation cohort (GSE84844) and excellent diagnostic performance (AUC=0.920). RT-qPCR validation in 65 pSS patients confirmed significantly elevated CASP1 mRNA expression in peripheral blood mononuclear cells versus controls (p<0.001). Single-cell sequencing (GSE214974) revealed CASP1 is specifically highly expressed in monocytes and dendritic cells. Expression positively correlated with IgA and IgM levels and associated with innate immune pathway activation including Toll-like receptors. Molecular docking demonstrated favorable binding between Dendrobium's active component 6-hydroxy-dendrobine and CASP1 protein. Clinical implications: CASP1 represents a potential diagnostic biomarker and therapeutic target, though functional validation studies are required to establish causality and therapeutic efficacy.